A Model for the Lateral Organization of Protein Molecules in Lipid Bilayers

Year: 1984 DOI: 10.7907/k7m9-xb92
Interactions between membrane bound proteins are examined using freeze-fracture etch electron microscopy. The pair distribution functions (PDF's) of protein particles in natural and synthetic membrane systems are examined, and compared with PDF's that are calculated from potential energy functions. In particular, PDF's calculated from the hard-disc only interaction between particles serve as a useful reference for determining whether particle interactions are attractive or repulsive. Of particular interest is the possibility that the lipid bilayer membrane mediates protein interactions. A model is presented for a lipid-mediated interaction that predicts that if protein molecules perturb the bilayer membrane away from its equilibrium (protein free) configuration and that if the perturbation is propagated laterally through the membrane over a sufficient distance, then an attractive interaction is the result.

The model is tested on recombinants of cytochrome c oxidase with dimyristoyl phosphatidyl choline and glycerol and with cardiolipin. Each recombinant is frozen from above the phase transition temperature of the lipid, so the membranes are expected to be fluid. Aggregation of protein into patches is seen, but all PDF's are indicative of a long-ranged repulsion. The model must be modified to account for the repulsion, a modification that would explain the observations in the inclusion of a vector membrane order parameter, namely lipid tilt, into the model. Tilt perturbation can be described by using the formalism already developed for describing nematic and smectic liquid crystals. A repulsive interaction between protein particles that is analogous to that seen between Schlieren textures in liquid crystals can be shown to occur if protein molecules induce tilt deformations in the bilayer around their boundaries.